Twenty-two novel mutations in the lysosomal α-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type II
Twenty-two novel mutations in the lysosomal α-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type II
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DOI：
10.1002/humu.10286
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发表时间：
2004-01-01
期刊：
影响因子：
3.9
通讯作者：
Reuser, AJJ
中科院分区：
文献类型：
--
作者：
Hermans, MMP;van Leenen, D;Reuser, AJJ
患有II型糖原累积病（GSDII，庞贝氏症）的患者由于酸性α-葡糖苷酶缺乏而遭受进行性肌无力。该病是一种常染色体隐性遗传，具有一系列临床表型。我们调查了29例GSDII，从而确定了55个致病突变的酸性α，葡萄糖苷酶基因（GAA）编码酸性麦芽糖酶。发现了34种不同的突变，其中22种是新的。所有的错义突变和其他两个突变与一个不可预测的影响酸性α-葡萄糖苷酶的合成和功能在COS细胞中瞬时表达。通过真实的时间PCR分析研究了新的剪接位点突变的影响。我们的分析结果强调了GSDII的临床表型在很大程度上取决于GAA等位基因突变的性质。这种基因型-表型相关性使DNA分析成为帮助预测疾病临床过程的有价值的工具。(C)2003 Wiley-Liss，Inc.
Patients with glycogen storage disease type II (GSDII, Pompe disease) suffer from progressive muscle weakness due to acid a-glucosidase deficiency. The disease is inherited as an autosomal recessive trait with a spectrum of clinical phenotypes. We have investigated 29 cases of GSDII and thereby identified 55 pathogenic mutations of the acid a,glucosidase gene (GAA) encoding acid maltase. There were 34 different mutations identified, 22 of which were novel. All of the missense mutations and two other mutations with an unpredictable effect on acid alpha-glucosidase synthesis and function were transiently expressed in COS cells. The effect of a novel splice-site mutation was investigated by real,time PCR analysis. The outcome of our analysis underscores the notion that the clinical phenotype of GSDII is largely dictated by the nature of the mutations in the GAA alleles. This genotype-phenotype correlation makes DNA analysis a valuable tool to help predict the clinical course of the disease. (C) 2003 Wiley-Liss, Inc.